Journal
GENETICS
Volume 210, Issue 1, Pages 171-187Publisher
GENETICS SOCIETY AMERICA
DOI: 10.1534/genetics.118.301031
Keywords
acentric; nuclear envelope; micronuclei; genome integrity
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Funding
- National Institutes of Health (NIH) [R01-GM-120321]
- NIH [5T32-GM-008646-18]
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While it is known that micronuclei pose a serious risk to genomic integrity by undergoing chromothripsis, mechanisms preventing micronucleus formation remain poorly understood. Here, we investigate how late-segregating acentric chromosomes that would otherwise form micronuclei instead reintegrate into daughter nuclei by passing through Aurora B kinase-dependent channels in the nuclear envelope of Drosophila melanogaster neuroblasts. We find that localized concentrations of Aurora B preferentially phosphorylate H3(S10) on acentrics and their associated DNA tethers. This phosphorylation event prevents HP1a from associating with heterochromatin and results in localized inhibition of nuclear envelope reassembly on endonuclease- and X-irradiation-induced acentrics, promoting channel formation. Finally, we find that HP1a also specifies initiation sites of nuclear envelope reassembly on undamaged chromatin. Taken together, these results demonstrate that Aurora B-mediated regulation of HP1a-chromatin interaction plays a key role in maintaining genome integrity by locally preventing nuclear envelope assembly and facilitating the incorporation of late-segregating acentrics into daughter nuclei.
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